Atherosclerotic cardiovascular disease

Last updated: November 30, 2023

Summarytoggle arrow icon

Atherosclerotic cardiovascular disease (ASCVD) is a group of conditions that are caused by atherosclerosis and that can affect different locations throughout the body. Examples of ASCVD include coronary artery disease (CAD), peripheral artery disease (PAD), and ischemic stroke. Major risk factors include advanced age, smoking, diabetes mellitus, hypertension, and dyslipidemia. The pathogenesis of atherosclerosis is precipitated by endothelial damage, which leads to inflammation and the formation of atheromas in vessel walls. The risk of ASCVD should be estimated using an ASCVD risk calculator like the pooled cohort equations (PCE) to guide timely primary prevention strategies, such as lifestyle modifications and prophylactic statin therapy. Management of ASCVD involves intensive lifestyle modifications and high-intensity statin therapy, with or without antiplatelet therapy, to minimize the risk of future cardiovascular events.

Atherosclerosistoggle arrow icon


The terms “arteriosclerosis” and “atherosclerosis” are often used synonymously.


Pathogenesis of atherosclerosis [2][3]

  1. Chronic stress on the endothelium (e.g., due to arterial hypertension and turbulence)
  2. Endothelial cell dysfunction, which leads to:
  3. Inflammation of the vessel wall
  4. Macrophages and SMCs ingest cholesterol from oxidized LDL; and transform into foam cells (macrophages filled with lipid droplets).
  5. Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
  6. Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) deposition → development of a fibrous plaque (atheroma)
  7. Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix minor stress ruptures the fibrous cap
  8. Calcification of the intima (the amount and pattern of calcification affect the risk of complications)
  9. Plaque rupture exposure of thrombogenic material ; (e.g., collagen) thrombus formation with vascular occlusion or spreading of thrombogenic material

Common sites (in order of frequency)

Atherosclerotic diseases [4]

Epidemiologytoggle arrow icon

  • Leading cause of vascular disease worldwide
  • >

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Traditional ASCVD risk factors [5]

These parameters are typically incorporated into ASCVD risk calculators such as PCE.

ASCVD risk-enhancing factors [1][6][7]

These parameters can be used to upwardly revise the risk assessment for patients with borderline or intermediate ASCVD risk. [8][9]

Risk assessmenttoggle arrow icon

ASCVD risk assessment is not recommended in individuals who are considered at high risk for ASCVD events, e.g., those with established ASCVD, familial hypercholesterolemia, and/or LDL cholesterol levels ≥ 190 mg/dL. [10]

General principles [6][10]

  • For adults aged 20–75 years with unknown ASCVD risk : [1][10]
  • Starting at age 20, reassess at least every 4–6 years.
  • Reassess more frequently in adults aged 40–75 years, depending on the individual ASCVD risk. [6][10][11]

Assessment for traditional ASCVD risk factors [5]

ASCVD risk calculation [1][10]

ASCVD risk calculators [5]

Risk calculators like the PCE should be used in patients at risk for ASCVD; they are not intended for patients with established ASCVD.

10-year ASCVD risk categories

The 10-year risk categories estimate the risk of developing myocardial infarction or stroke in this time period and are used for individuals aged 40–75 years. [10]

  • Low risk: < 5%
  • Borderline risk: 5–7.4%
  • Intermediate risk: 7.5–19.9%
  • High risk: ≥ 20%

Additional evaluation [1]

In patients with borderline or intermediate ASCVD risk, results from the following studies may help shared decision-making regarding preventive statin therapy.

Assessment for ASCVD risk-enhancing factors [1]

Low-dose cardiac CT scan [10][13]

Although ASCVD risk calculators are important tools for guiding primary prevention strategies in individuals with no history of ASCVD, results should always be considered in conjunction with other factors, e.g., ASCVD risk-enhancing factors, CAC scoring, and patient preferences.

Primary preventiontoggle arrow icon

General principles [10][14]

Lifestyle modifications for ASCVD prevention [6][10]

Smoking cessation is one of the most effective interventions to reduce all-cause mortality and prevent recurrent vascular events in patients with ASCVD! [16]

Pharmacological prevention [10]

Recommendations for preventive therapy vary.

Preventive statins

Indications for statins for primary ASCVD prevention
2019 American Heart association (AHA) guideline on primary prevention of cardiovascular disease [1][10] 2022 USPSTF recommendation on statin use for primary prevention of cardiovascular disease [11]
Age 20–39 years
  • N/A
Age 40–75 years

Preventive aspirin [10][17]

Consider only for patients with a low risk of bleeding, and use shared decision-making.

Aspirin for primary prevention of ASCVD is contraindicated in individuals at increased risk of bleeding.

Remember the ABCDS of ASCVD primary prevention: Aspirin (if there are indications), Blood pressure control, Cholesterol management, Diabetes management, Smoking cessation. [14]

Managementtoggle arrow icon

This section provides an overview of long-term management strategies for ASCVD. See respective articles for specific treatment of an acute ASCVD events, e.g., management of ischemic stroke.

General principles [1][6]

Risk assessment for recurrent ASCVD events [1][10]

Patients with ASCVD are considered at very high risk of future ASCVD events in the following scenarios:

Lipid-lowering therapy for ASCVD

Statin therapy [1]

Treatment to a specific LDL cholesterol goal (e.g., < 70 mg/dL) vs. targeting statin intensity is a topic of ongoing inquiry. [1][6]

Overview of statin intensity [1]

Intensity Agents

High-intensity statin therapy

Moderate-intensity statin therapy
Low-intensity statin therapy

Nonstatin lipid-lowering agents [1]

Antiplatelet therapy

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Referencestoggle arrow icon

  1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; 139 (25).doi: 10.1161/cir.0000000000000625 . | Open in Read by QxMD
  2. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk. Circulation. 2013; 129 (25_suppl_2): p.S49-S73.doi: 10.1161/01.cir.0000437741.48606.98 . | Open in Read by QxMD
  3. Handelsman Y, Jellinger PS, Guerin CK, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Management of Dyslipidemia and Prevention of Cardiovascular Disease Algorithm – 2020 Executive Summary. Endocr Pract. 2020; 26 (10): p.1196-1224.doi: 10.4158/cs-2020-0490 . | Open in Read by QxMD
  4. Kershaw KN, Lane-Cordova AD, Carnethon MR, Tindle HA, Liu K. Chronic Stress and Endothelial Dysfunction: The Multi-Ethnic Study of Atherosclerosis (MESA). Am J Hypertens. 2016; 30 (1): p.75-80.doi: 10.1093/ajh/hpw103 . | Open in Read by QxMD
  5. Donald M. Lloyd-Jones, Lynne T. Braun, Chiadi E. Ndumele, Sidney C. Smith, Laurence S. Sperling, Salim S. Virani, Roger S. Blumenthal. Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology. Circulation. 2019; 139 (25).doi: 10.1161/cir.0000000000000638 . | Open in Read by QxMD
  6. Agarwala A, Liu J, Ballantyne CM, Virani SS. The Use of Risk-Enhancing Factors to Personalize ASCVD Risk Assessment: Evidence and Recommendations from the 2018 AHA/ACC Multi-Society Cholesterol Guidelines. Curr Cardiovasc Risk Rep. 2019; 13 (7).doi: 10.1007/s12170-019-0616-y . | Open in Read by QxMD
  7. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. J Am Coll Cardiol. 2019; 74 (10): p.e177-e232.doi: 10.1016/j.jacc.2019.03.010 . | Open in Read by QxMD
  8. Mangione CM, Barry MJ, et al. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. JAMA. 2022; 328 (8): p.746.doi: 10.1001/jama.2022.13044 . | Open in Read by QxMD
  9. Burke G, Lima J, Wong ND, Narula J. The Multiethnic Study of Atherosclerosis. Glob Heart. 2016; 11 (3): p.267.doi: 10.1016/j.gheart.2016.09.001 . | Open in Read by QxMD
  10. Ghoshhajra BB, Hedgire SS, Hurwitz Koweek LM, et al. ACR Appropriateness Criteria® Asymptomatic Patient at Risk for Coronary Artery Disease: 2021 Update. J Am Coll Radiol. 2021; 18 (5): p.S2-S12.doi: 10.1016/j.jacr.2021.01.003 . | Open in Read by QxMD
  11. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017; 135 (12).doi: 10.1161/cir.0000000000000471 . | Open in Read by QxMD
  12. Hackam DG, Spence JD. Antiplatelet Therapy in Ischemic Stroke and Transient Ischemic Attack. Stroke. 2019; 50 (3): p.773-778.doi: 10.1161/strokeaha.118.023954 . | Open in Read by QxMD
  13. Smith SC, Benjamin EJ, Bonow RO, et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update. Circulation. 2011; 124 (22): p.2458-2473.doi: 10.1161/cir.0b013e318235eb4d . | Open in Read by QxMD
  14. Payal Kohli, Seamus P. Whelton, Steven Hsu, Clyde W. Yancy, Neil J. Stone, Jonathan Chrispin, Nisha A. Gilotra, Brian Houston, M. Dominique Ashen, Seth S. Martin, Parag H. Joshi, John W. McEvoy, Ty J. Gluckman, Erin D. Michos, et al.. Clinician's Guide to the Updated ABCs of Cardiovascular Disease Prevention. Journal of the American Heart Association. 2014; 3 (5): p.e001098.doi: 10.1161/jaha.114.001098 . | Open in Read by QxMD
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  16. Goljan EF. Rapid Review Pathology. Elsevier Saunders ; 2018
  17. Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nature Reviews Disease Primers. 2019; 5 (1).doi: 10.1038/s41572-019-0106-z . | Open in Read by QxMD
  18. Lloyd-Jones DM, Huffman MD, Karmali KN, et al. Estimating Longitudinal Risks and Benefits From Cardiovascular Preventive Therapies Among Medicare Patients: The Million Hearts Longitudinal ASCVD Risk Assessment Tool: A Special Report From the American Heart Association and American College of Cardiology. Circulation. 2017; 135 (13).doi: 10.1161/cir.0000000000000467 . | Open in Read by QxMD
  19. Snetselaar LG, de Jesus JM, DeSilva DM, Stoody EE. Dietary Guidelines for Americans, 2020–2025. Nutr Today. 2021; 56 (6): p.287-295.doi: 10.1097/nt.0000000000000512 . | Open in Read by QxMD
  20. Van den Berg MJ, van der Graaf Y, Deckers JW, et al. Smoking cessation and risk of recurrent cardiovascular events and mortality after a first manifestation of arterial disease. Am Heart J. 2019; 213: p.112-122.doi: 10.1016/j.ahj.2019.03.019 . | Open in Read by QxMD
  21. Davidson KW, Barry MJ, et al. Aspirin Use to Prevent Cardiovascular Disease. JAMA. 2022; 327 (16): p.1577.doi: 10.1001/jama.2022.4983 . | Open in Read by QxMD

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